Appendix 1. Electronic search strategy

Database searches

Cochrane Central Register of Controlled Trials (CENTRAL)

Wiley http://onlinelibrary.wiley.com/

Issue 8 of 12, August 2014

Searched on 22^nd September 2014. 70 records were retrieved.

1. MeSH descriptor: [Infant, Newborn] explode all trees 13194

2. MeSH descriptor: [Premature Birth] this term only 397

3. (neonat* or neo next nat*):ti,ab,kw 10126

4. (newborn* or new next born* or newly next born*):ti,ab,kw 16527

5. (preterm or preterms or pre next term or pre next terms):ti,ab,kw 6017

6. (preemie* or premie or premies):ti,ab,kw 14

7. (prematur* near/3 (birth* or born or deliver*)):ti,ab,kw 1126

8. (low near/3 (birthweight* or birth next weight*)):ti,ab,kw 3243

9. (lbw or vlbw or elbw):ti,ab,kw 887

10. infan*:ti,ab,kw 36861

11. (baby or babies):ti,ab,kw 3163

12. MeSH descriptor: [Enterocolitis, Necrotizing] this term only 121

13. enterocolitis:ti,ab,kw 683

14. NEC:ti,ab,kw 173

15. #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 43510

16. MeSH descriptor: [Glutamine] this term only 491

17. glutam*:ti,ab,kw 3181

18. levoglutam*:ti,ab,kw 0

19. #16 or #17 or #18 3181

20. #15 and #19 189

21. #15 and #19 in Trials 186

22. #15 and #19 Publication Year from 2007 to 2014, in Trials 70

Key

MeSH descriptor = indexing term (MeSH heading)

* = truncation

:ti,ab,kw = terms in either title or abstract or keyword fields

near/3 = terms within three words of each other (any order)

next = terms are next to each other

EMBASE

OvidSP http://ovidsp.ovid.com/

1980 to 2014 Week 38

Searched on 22^nd September 2014. 87 records were retrieved. A search strategy developed by Lefebvre 2008 to identify randomised trials in EMBASE was used to limit retrieval to clinical trials (lines 22‐36).

1. exp infant/ (841476)

2. prematurity/ (70117)

3. premature labor/ (29157)

4. exp low birth weight/ (39329)

5. (neonat$ or neo nat$).ti,ab. (229859)

6. (newborn$ or new born$ or newly born$).ti,ab. (143427)

7. (preterm or preterms or pre term or pre terms).ti,ab. (60787)

8. (preemie$ or premie or premies).ti,ab. (154)

9. (prematur$ adj3 (birth$ or born or deliver$)).ti,ab. (14127)

10. (low adj3 (birthweight$ or birth weight$)).ti,ab. (29286)

11. (lbw or vlbw or elbw).ti,ab. (6941)

12. infan$.ti,ab. (364930)

13. (baby or babies).ti,ab. (64354)

14. necrotizing enterocolitis/ (6320)

15. enterocolitis.ti,ab. (9685)

16. NEC.ti,ab. (4115)

17. or/1‐16 (1134787)

18. glutamine/ (28305)

19. glutam$.ti,ab. (162556)

20. levoglutam$.ti,ab. (3)

21. 18 or 19 or 20 (173526)

22. random$.ti,ab. (900117)

23. factorial$.ti,ab. (23315)

24. crossover$.ti,ab. (49098)

25. cross‐over$.ti,ab. (21608)

26. placebo$.ti,ab. (202020)

27. (doubl$ adj blind$).ti,ab. (143459)

28. (singl$ adj blind$).ti,ab. (14632)

29. assign$.ti,ab. (242053)

30. allocat$.ti,ab. (85229)

31. volunteer$.ti,ab. (177796)

32. Crossover Procedure/ (40222)

33. double blind procedure/ (115438)

34. Randomized Controlled Trial/ (350056)

35. single blind procedure/ (18827)

36. or/22‐35 (1432268)

37. 17 and 21 and 36 (364)

38. animal/ (1570185)

39. exp animal experiment/ (1697956)

40. Nonhuman/ (4374620)

41. (rat or rats or mouse or mice or hamster or hamsters or animal or animals or dog or dogs or cat or cats or bovine or sheep).ti,ab,sh. (4568271)

42. 38 or 39 or 40 or 41 (6746352)

43. exp human/ (15016996)

44. human experiment/ (329080)

45. 43 or 44 (15018382)

46. 42 not (42 and 45) (5182957)

47. 37 not 46 (225)

48. limit 47 to em=201100‐201438 (87)

Key:

/ = indexing term (EMTREE heading)

$ = truncation

.ti,ab. = terms in either title or abstract fields

adj3 = terms within three words of each other (any order)

.sh.= subject heading field

.em. = entry date – date added to database

Maternity and Infant Care

OvidSP http://ovidsp.ovid.com/

1971 to August 2014

Searched on 22^nd September 2014. 59 records were retrieved.

1. Infant.de. (7384)

2. Infant ‐ newborn.de. (23849)

3. Infant ‐ premature.de. (7331)

4. infant ‐ very premature.de. (753)

5. Infant ‐ low birth weight.de. (2367)

6. Infant ‐ very low birth weight.de. (2147)

7. Premature birth.de. (1625)

8. Infant ‐ small for gestational age.de. (887)

9. (neonat$ or neo nat$).ti,ab. (32059)

10. (newborn$ or new born$ or newly born$).ti,ab. (14916)

11. (preterm or preterms or pre term or pre terms).ti,ab. (18476)

12. (preemie$ or premie or premies).ti,ab. (41)

13. (prematur$ adj3 (birth$ or born or deliver$)).ti,ab. (3141)

14. (low adj3 (birthweight$ or birth weight$)).ti,ab. (8455)

15. (lbw or vlbw or elbw).ti,ab. (2237)

16. infan$.ti,ab. (48220)

17. (baby or babies).ti,ab. (23514)

18. Enterocolitis.de. (8)

19. enterocolitis.ti,ab. (1349)

20. NEC.ti,ab. (493)

21. or/1‐20 (94518)

22. Glutamine.de. (16)

23. glutam$.ti,ab. (161)

24. levoglutam$.ti,ab. (0)

25. 22 or 23 or 24 (162)

26. 21 and 25 (108)

27. limit 26 to yr="2007 ‐Current" (59)

Key

.de. = indexing term

$ = truncation

.ti,ab. = terms in either title or abstract fields

adj3 = terms within three words of each other (any order)

yr = year published

MEDLINE

OvidSP http://ovidsp.ovid.com/

1946 to September week 2 2014

Searched on 22^nd September 2014. 61 records were retrieved. The Cochrane highly sensitive search strategy for identifying randomized trials in MEDLINE (sensitivity‐maximizing version) was used to limit retrieval to clinical trials (lines 21‐31) (Lefebvre 2011).

1. exp Infant, Newborn/ (504876)

2. Premature Birth/ (6949)

3. (neonat$ or neo nat$).ti,ab. (189942)

4. (newborn$ or new born$ or newly born$).ti,ab. (128353)

5. (preterm or preterms or pre term or pre terms).ti,ab. (45250)

6. (preemie$ or premie or premies).ti,ab. (106)

7. (prematur$ adj3 (birth$ or born or deliver$)).ti,ab. (11353)

8. (low adj3 (birthweight$ or birth weight$)).ti,ab. (24580)

9. (lbw or vlbw or elbw).ti,ab. (5285)

10. infan$.ti,ab. (323868)

11. (baby or babies).ti,ab. (50568)

12. Enterocolitis, Necrotizing/ (2030)

13. enterocolitis.ti,ab. (7862)

14. NEC.ti,ab. (2655)

15. or/1‐14 (818716)

16. Glutamine/ (15076)

17. glutam$.ti,ab. (145071)

18. levoglutam$.ti,ab. (4)

19. 16 or 17 or 18 (149488)

20. 15 and 19 (5020)

21. randomized controlled trial.pt. (388375)

22. controlled clinical trial.pt. (89809)

23. randomized.ab. (284414)

24. placebo.ab. (150745)

25. drug therapy.fs. (1744932)

26. randomly.ab. (201022)

27. trial.ab. (295504)

28. groups.ab. (1282228)

29. or/21‐28 (3283677)

30. exp animals/ not humans.sh. (4011372)

31. 29 not 30 (2797292)

32. 15 and 19 and 31 (437)

33. limit 32 to ed=20111101‐20140911 (61)

Key

/ = indexing term (MeSH heading)

exp = exploded MeSH heading

$ = truncation

.ti,ab. = terms in either title or abstract fields

adj3 = terms within three words of each other (any order)

.pt. = publication type

.fs. = floating subheading

.sh.= subject heading

.ed. = entry date ‐ date added to the database

MEDLINE In‐Process & Other Non‐Indexed Citations

OvidSP http://ovidsp.ovid.com/

September 19, 2014

Searched on 22^nd September 2014. 60 records were retrieved.

1. exp Infant, Newborn/ (0)

2. Premature Birth/ (0)

3. (neonat$ or neo nat$).ti,ab. (10428)

4. (newborn$ or new born$ or newly born$).ti,ab. (5627)

5. (preterm or preterms or pre term or pre terms).ti,ab. (3486)

6. (preemie$ or premie or premies).ti,ab. (11)

7. (prematur$ adj3 (birth$ or born or deliver$)).ti,ab. (623)

8. (low adj3 (birthweight$ or birth weight$)).ti,ab. (1523)

9. (lbw or vlbw or elbw).ti,ab. (432)

10. infan$.ti,ab. (16416)

11. (baby or babies).ti,ab. (3393)

12. Enterocolitis, Necrotizing/ (0)

13. enterocolitis.ti,ab. (468)

14. NEC.ti,ab. (298)

15. or/1‐14 (30053)

16. Glutamine/ (0)

17. glutam$.ti,ab. (8117)

18. levoglutam$.ti,ab. (0)

19. 16 or 17 or 18 (8117)

20. 15 and 19 (176)

21. limit 20 to ed=20111101‐20140918 (60)

Key

/ = indexing term (MeSH heading)

exp = exploded MeSH heading

$ = truncation

.ti,ab. = terms in either title or abstract fields

adj3 = terms within three words of each other (any order)

ed = entry date ‐ date added to the database

PubMed

http://www.ncbi.nlm.nih.gov/pubmed/

Searched on 23^rd September 2014. 82 records were retrieved. The Cochrane highly sensitive search strategy for identifying randomized trials in PubMed (sensitivity‐maximizing version) was used to limit retrieval to clinical trials (Lefebvre 2011).

Search (((((((((((((((((((((("Infant, Newborn"[Mesh])) OR ("Premature Birth"[Mesh])) OR (((neonat*[Title/Abstract]) OR neo nat*[Title/Abstract]) OR neo‐nat*[Title/Abstract])) OR (((((newborn*[Title/Abstract]) OR new born*[Title/Abstract]) OR new‐born*[Title/Abstract]) OR newly born*[Title/Abstract]) OR newly‐born*[Title/Abstract])) OR ((((((preterm[Title/Abstract]) OR preterms[Title/Abstract]) OR pre term[Title/Abstract]) OR pre‐term[Title/Abstract]) OR pre terms[Title/Abstract]) OR pre‐terms[Title/Abstract])) OR (((preemie*[Title/Abstract]) OR premie[Title/Abstract]) OR premies[Title/Abstract])) OR ((prematur*[Title/Abstract]) AND birth*[Title/Abstract])) OR ((prematur*[Title/Abstract]) AND born[Title/Abstract])) OR ((prematur*[Title/Abstract]) AND deliver*[Title/Abstract])) OR ((low[Title/Abstract]) AND birthweight*[Title/Abstract])) OR ((low[Title/Abstract]) AND birth weight*[Title/Abstract])) OR ((low[Title/Abstract]) AND birth‐weight*[Title/Abstract])) OR (((lbw[Title/Abstract]) OR vlbw[Title/Abstract]) OR elbw[Title/Abstract])) OR (infan*[Title/Abstract])) OR ((baby[Title/Abstract]) OR babies[Title/Abstract])) OR ("Enterocolitis, Necrotizing"[Mesh:noexp]) OR (enterocolitis[Title/Abstract]) OR (NEC[Title/Abstract]))) AND (((levoglutam*[Title/Abstract]) OR glutam*[Title/Abstract]) OR "Glutamine"[Mesh:noexp]))) AND (((((((((((randomized controlled trial[Publication Type])) OR (controlled clinical trial[Publication Type])) OR (randomized[Title/Abstract])) OR (placebo[Title/Abstract])) OR (drug therapy[MeSH Subheading])) OR (randomly[Title/Abstract])) OR (trial[Title/Abstract])) OR (groups[Title/Abstract]))) NOT (animals[mh] NOT humans[mh])))) AND ("2011/11/01"[Date ‐ Entrez] : "3000"[Date ‐ Entrez])

Key

[Mesh] = exploded Medical Subject heading (MeSH)

[mh] = exploded MeSH

[Mesh:noexp] = MeSH not exploded

* = truncation

[Title/Abstract] = terms in either title or abstract fields

[Date ‐ Entrez] = entry date ‐ date added to the database

Trial register searches

Clinical Trials.gov

http://clinicaltrials.gov/

Searched on 23^rd September 2014. 17 records were retrieved in total using the following search strategies:

4 studies found for: Glutamine AND (infant OR infants OR newborn OR newborns OR premature OR prematurity OR neonate OR neonates OR neonatal OR preterm OR preterms OR preemie OR preemies OR premie OR premies OR birthweight OR baby OR babies) | received on or after 11/01/2011 | updated on or after 11/01/2011

1 study found for: Glutamine AND (NEC OR enterocolitis) | received on or after 11/01/2011 | updated on or after 11/01/2011

12 studies found for: "Glutamine" | Child | received on or after 11/01/2011 | updated on or after 11/01/2011

metaRegister of Controlled Trials (mRCT)

http://www.controlled‐trials.com/mrct/searchform

Searched on 23^rd September 2014. 18 trials were retrieved.

(Glutamine AND (infant OR infants OR newborn OR newborns OR premature OR prematurity OR neonate OR neonates or neonatal OR preterm OR preterms OR preemie OR preemies OR premie OR premies OR birthweight OR baby OR babies OR enterocolitis or NEC))

WHO International Clinical Trials Registry Platform

http://apps.who.int/trialsearch/AdvSearch.aspx

Searched on 23^rd September 2014. 21 trials were retrieved in total using the following search strategies:

1. glutam* in title, clinical trials in children – 11 trials.

2. glutam* in intervention field, clinical trials in children – 10 trials.